scholarly journals Advances in understanding cartilage remodeling

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 642 ◽  
Author(s):  
Yefu Li ◽  
Lin Xu
Keyword(s):  
Articular Cartilage ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Cartilage Destruction ◽  
Significant Progress ◽  
Loss Of Balance ◽  
Growth Factor Beta ◽  
Articular Cartilage Degeneration ◽  
Made In

Cartilage remodeling is currently among the most popular topics in osteoarthritis research. Remodeling includes removal of the existing cartilage and replacement by neo-cartilage. As a loss of balance between removal and replacement of articular cartilage develops (particularly, the rate of removal surpasses the rate of replacement), joints will begin to degrade. In the last few years, significant progress in molecular understanding of the cartilage remodeling process has been made. In this brief review, we focus on the discussion of some current “controversial” observations in articular cartilage degeneration: (1) the biological effect of transforming growth factor-beta 1 on developing and mature articular cartilages, (2) the question of whether aggrecanase 1 (ADAMTS4) and aggrecanase 2 (ADAMTS5) are key enzymes in articular cartilage destruction, and (3) chondrocytes versus chondron in the development of osteoarthritis. It is hoped that continued discussion and investigation will follow to better clarify these topics. Clarification will be critical for those in search of novel therapeutic targets for the treatment of osteoarthritis.

A Molecular Cascade Underlying Articular Cartilage Degeneration

2020 ◽  
Vol 21 (9) ◽  
pp. 838-848 ◽  
Author(s):  
Lin Xu ◽  
Yefu Li
Keyword(s):  
Articular Cartilage ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Cartilage Destruction ◽  
Cell Surface Receptor ◽  
Molecular Events ◽  
Surface Receptor ◽  
A Cell ◽  
Articular Cartilage Degeneration

Preserving of articular cartilage is an effective way to protect synovial joints from becoming osteoarthritic (OA) joints. Understanding of the molecular basis of articular cartilage degeneration will provide valuable information in the effort to develop cartilage preserving drugs. There are currently no disease-modifying OA drugs (DMOADs) available to prevent articular cartilage destruction during the development of OA. Current drug treatments for OA focus on the reduction of joint pain, swelling, and inflammation at advanced stages of the disease. However, based on discoveries from several independent research laboratories and our laboratory in the past 15 to 20 years, we believe that we have a functional molecular understanding of articular cartilage degeneration. In this review article, we present and discuss experimental evidence to demonstrate a sequential chain of the molecular events underlying articular cartilage degeneration, which consists of transforming growth factor beta 1, high-temperature requirement A1 (a serine protease), discoidin domain receptor 2 (a cell surface receptor tyrosine kinase for native fibrillar collagens), and matrix metalloproteinase 13 (an extracellularmatrix degrading enzyme). If, as we strongly suspect, this molecular pathway is responsible for the initiation and acceleration of articular cartilage degeneration, which eventually leads to progressive joint failure, then these molecules may be ideal therapeutic targets for the development of DMOADs.

MOLECULAR CONTROL OF ARTICULAR CARTILAGE DEGENERATION BY TRANSFORMING GROWTH FACTOR ALPHA

2008 ◽  
Vol 31 (4) ◽  
pp. 2
Author(s):  
Tom Appleton ◽  
Shirine Usmani ◽  
John Mort ◽  
Frank Beier
Keyword(s):  
Gene Expression ◽  
Articular Cartilage ◽  
Growth Factor ◽  
P38 Mapk ◽  
Transforming Growth Factor ◽  
Cartilage Degeneration ◽  
Signalling Pathways ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha ◽  
Articular Cartilage Degeneration

Background: Articular cartilage degeneration is a hallmark of osteoarthritis (OA). We previously identified increased expression of transforming growth factor alpha (TGF?) and chemokine (C-C motif) ligand 2 (CCL2) in articular cartilage from a rat modelof OA (1,2). We subsequently reported that TGF? signalling modified chondrocyte cytoskeletal organization, increased catabolic and decreased anabolic gene expression and suppressed Sox9. Due to other roles in chondrocytes, we hypothesized that the effects ofTGF? on chondrocytes are mediated by Rho/ROCK and MEK/ERK signaling pathways. Methods: Primary cultures of chondrocytes and articularosteochondral explants were treated with pharmacological inhibitors of MEK1/2(U0126), ROCK (Y27632), Rho (C3), p38 MAPK (SB202190) and PI3K (LY294002) to elucidate pathway involvement. Results: Using G-LISA we determined that stimulation of primary chondrocytes with TGF? activates RhoA. Reciprocally, inhibition of RhoA/ROCK but not other signalling pathways prevents modification of the actin cytoskeleton in responseto TGF?. Inhibition of MEK/ERKsignaling rescued suppression of anabolic gene expression by TGF? including SOX9 mRNA and protein levels. Inhibition of MEK/ERK, Rho/ROCK, p38 MAPK and PI3K signalling pathways differentially controlled the induction of MMP13 and TNF? gene expression. TGF? also induced expression of CCL2 specifically through MEK/ERK activation. In turn, CCL2 treatment induced the expression of MMP3 and TNF?. Finally, we assessed cartilage degradation by immunohistochemical detection of type II collagen cleavage fragments generated by MMPs. Blockade of RhoA/ROCK and MEK/ERK signalling pathways reduced the generation of type IIcollagen cleavage fragments in response to TGF? stimulation. Conclusions: Rho/ROCK signalling mediates TGF?-induced changes inchondrocyte morphology, while MEK/ERK signalling mediates the suppression ofSox9 and its target genes, and CCL2 expression. CCL2, in turn, induces the expression of MMP3 and TNF?, two potent catabolic factors known to be involved in OA. These pathways may represent strategic targets for interventional approaches to treating cartilage degeneration in osteoarthritis. References: 1. Appleton CTG et al. Arthritis Rheum 2007;56:1854-68. 2. Appleton CTG et al. Arthritis Rheum 2007; 56:3693-705.

scholarly journals Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1)

2018 ◽  
Vol 7 (11) ◽  
pp. 587-594 ◽  
Author(s):  
R-K. Zhang ◽  
G-W. Li ◽  
C. Zeng ◽  
C-X. Lin ◽  
L-S. Huang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Growth Factor ◽  
Cyclic Loading ◽  
Mechanical Stress ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cartilage Degradation ◽  
Growth Factor Beta ◽  
Tgf Β1 ◽  
Cultured Chondrocytes

Objectives The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1.

The Expression of IL-1, IL-6, and TGF-β in the Synovial Fluid of Horses with Surgically-Induced Transient Synovitis

1998 ◽  
Vol 11 (03) ◽  
pp. 141-145 ◽  
Author(s):  
S. M. Barber ◽  
J. R. Gordon ◽  
Christine Theoret
Keyword(s):  
Articular Cartilage ◽  
Growth Factor ◽  
Synovial Fluid ◽  
Transforming Growth Factor Beta ◽  
Interleukin 6 ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Transient Synovitis ◽  
Growth Factor Beta ◽  
Surgically Induced

SummaryThis study investigates the presence of various cytokines in the synovial fluid of three horses with surgicallyinduced synovitis in one antebrachiocarpal joint. Synovial fluids were sampled from experimental and control joints, preoperatively and at two and 30 days post-operatively. Samples were analyzed for interleukin-1 and interleukin- 6 bioactivities with a bioassay, and for transforming growth factor-beta protein by ELISA. Peak cytokine levels were detected on day two post-synovectomy, and returned to pre-operative levels by 30 days post-synovectomy (Interleukin-6 in treated joints: day #0; 0.53 ±0.2, day #2; 9.8 ± 0.7, day #30; 0.4 ± 0.2. Transforming growth factorbeta in treated joints: day #0; 314 ± 69, day #2; 1101 ± 325, day #30; 321 ± 101). Arthrocentesis alone (i.e. control joints) caused no increase in interleukin- 1, interleukin-6 and transforming growth factor-beta levels. Interleukin-1 and interleukin-6 are thought to both prevent anabolic and enhance catabolic effects within articular cartilage matrices, whereas it has been proposed that transforming growth factor-beta may have a protective effect on the articular cartilage. This study is the first to document elevated transforming growth factor-beta levels in equine joints.This study documents elevated levels of transforming growth factor-beta, interleukin-1 and interleukin-6 in the joints of horses with surgically-induced transient synovitis.

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